XMM-Newton and Optical Observations of Cataclysmic Variables from SDSS

We report on XMM-Newton and optical results for 6 cataclysmic variables that were selected from Sloan Digital Sky Survey spectra because they showed strong HeII emission lines, indicative of being candidates for containing white dwarfs with strong magnetic fields. While high X-ray background rates prevented optimum results, we are able to confirm SDSSJ233325.92+152222.1 as an intermediate polar from its strong pulse signature at 21 min and its obscured hard X-ray spectrum. Ground-based circular polarization and photometric observations were also able to confirm SDSSJ142256.31-022108.1 as a polar with a period near 4 hr. Photometry of SDSSJ083751.00+383012.5 and SDSSJ093214.82+495054.7 solidifies the orbital period of the former as 3.18 hrs and confirms the latter as a high inclination system with deep eclipses.Comment: 31 pages, 14 figures. Accepted for publication in the Astronomical Journa

Post-traumatic osteoarthritis in mice following mechanical injury to the synovial joint

We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention

Localizing Transcriptional Regulatory Elements at the Mouse Dlk1 Locus

Much effort has focused recently on determining the mechanisms that control the allele-specific expression of genes subject to genomic imprinting, yet imprinting regulation is only one aspect of configuring appropriate expression of these genes. Imprinting control mechanisms must interact with those regulating the tissue-specific expression pattern of each imprinted gene in a cluster. Proper expression of the imprinted Delta-like 1 (Dlk1) - Maternally expressed gene 3 (Meg3) gene pair is required for normal fetal development in mammals, yet the mechanisms that control tissue-specific expression of these genes are unknown. We have used a combination of in vivo and in vitro expression assays to localize cis-regulatory elements that may regulate Dlk1 expression in the mouse embryo. A bacterial artificial chromosome transgene encompassing the Dlk1 gene and 77 kb of flanking sequence conferred expression in most endogenous Dlk1-expressing tissues. In combination with previous transgenic data, these experiments localize the majority of Dlk1 cis-regulatory elements to a 41 kb region upstream of the gene. Cross-species sequence conservation was used to further define potential regulatory elements, several of which functioned as enhancers in a luciferase expression assay. Two of these elements were able to drive expression of a lacZ reporter transgene in Dlk1-expressing tissues in the mouse embryo. The sequence proximal to Dlk1 therefore contains at least two discrete regions that may regulate tissue-specificity of Dlk1 expression

A case of acute myeloid leukemia with promyelocytic features characterized by expression of a novel RARG-CPSF6 fusion

Key Points Novel RARG-CPSF6 fusion in an AML case with promyelocytic features and no evidence of PML-RARA or X-RARA fusion. Gene fusions involving RARG can initiate AML with promyelocytic morphological features.</jats:p

The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma, but does not prevent tumor growth

A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 μg/l (normal <0.2) and within 2 days 3 × 200 μg octreotide daily suppressed plasma glucagon to 2.2-2.5 μg/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal <0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very highdosesof octreotide (4 × 600 μg/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies

Substitutions of red meat, poultry and fish and risk of myocardial infarction

AbstractRed meat has been suggested to be adversely associated with risk of myocardial infarction (MI), but previous studies have rarely taken replacement foods into consideration. We aimed to investigate optimal substitutions between and within the food groups of red meat, poultry and fish for MI prevention. We followed up 55 171 women and men aged 50–64 years with no known history of MI at recruitment. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for specified food substitutions of 150 g/week. During a median follow-up time of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for replacing red meat with fatty fish was 0·76 (95 % CI 0·64, 0·89), whereas the HR for replacing red meat with lean fish was 1·00 (95 % CI 0·89, 1·14). Similarly, replacing poultry with fatty but not lean fish was inversely associated with MI: the HR was 0·81 (95 % CI 0·67, 0·98) for fatty fish and was 1·08 (95 % CI 0·92, 1·27) for lean fish. The HR for replacing lean with fatty fish was 0·75 (95 % CI 0·60, 0·94). Replacing processed with unprocessed red meat was not associated with MI. Among men, a similar pattern was found, although the associations were not statistically significant. This study suggests that replacing red meat, poultry or lean fish with fatty fish is associated with a lower risk of MI.</jats:p

Substitution of meat and fish with vegetables or potatoes and risk of myocardial infarction

AbstractRed meat has been suggested to be adversely associated with risk of myocardial infarction (MI), whereas vegetable consumption has been found to be protective. The aim of this study was to investigate substitutions of red meat, poultry and fish with vegetables or potatoes for MI prevention. We followed up 29 142 women and 26 029 men in the Danish Diet, Cancer and Health study aged 50–64 years with no known history of MI at baseline. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for MI associated with specified food substitutions of 150 g/week. During a median follow-up of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for MI when replacing red meat with vegetables was 0·94 (95 % CI 0·90, 0·98). Replacing fatty fish with vegetables was associated with a higher risk of MI (HR 1·23; 95 % CI 1·05, 1·45), whereas an inverse, statistically non-significant association was found for lean fish (HR 0·93; 95 % CI 0·83, 1·05). Substituting poultry with vegetables was not associated with risk of MI (HR 1·00; 95 % CI 0·90, 1·11). Findings for substitution with potatoes were similar to findings for vegetables. Among men, a similar pattern was observed, but the associations were weak and mostly statistically non-significant. This study suggests that replacing red meat with vegetables or potatoes is associated with a lower risk of MI, whereas replacing fatty fish with vegetables or potatoes is associated with a higher risk of MI.</jats:p